This invention relates to stabilized urea (carbamide) compositions in various pharmaceutical and cosmetic preparations, and more particularly to such compositions stabilized by the addition of a lactone, preferably gamma-butyrolactone.
The value of urea in pharmaceutical and cosmetic preparations has been recognized since the early days of folk medicine. It is known that 10-30 percent urea is mildly keratolytic and increases water uptake in the stratum corneum. This gives it a high water-binding capacity which leads to the use of urea as a skin moisturizer, or as a transdermal drug penetration enhancer. Urea also aids in debridement, dissolves the coagulum and promotes epithelialization when used in a concentration of approximately 10-15 percent. At higher concentrations, e.g. above 40 percent, urea is proteolytic and therefore, is used for the treatment of nail destruction and dissolution. Furthermore for treatment for mobilization of edema fluid, urea is used as an osmotic diuretic. Nevertheless, urea has been found to be unsuitable in many pharmaceutical and cosmetic preparations because it tends to be unstable, with the urea hydrolyzing into ammonium cyanate. Although the degree of urea degradation is generally small, the untoward effects, such as ammoniacal odor and pH shift to alkali, can be very sifignificant. The ammoniacal odor and increased pH are known to result from ammonia production, which occurs in the following manner when urea is present: ##STR1##
To cope with the adverse effects caused by urea degradation, numerous attempts were made in the past to stabilize the urea preparation through the use of buffers or acids to neutralize the ammonia produced by urea breakdown. These methods have not been very satisfactory, however, because the acidification tends to accelerate the process of decomposition. Another problem in the use of acidic preparations in pharmaceutical and cosmetic products has been the burning or stinging sensation that occurs when topical preparations containing urea are applied to the skin.